The Cancer Degradome
Proteolysis is essential for life. From the breakdown of proteins in food for biosynthesis, through to antigen processing in the immune system, the blood cl- ting cascade, and the hormone-regulated remodelling of female reproductive tissues in adult mammals – proteolysis governs functionality, homeostasis, and fate at the levels of the cell and the entire organism. For the cancer cell, intracellular prote- ysis carried out by caspases and the proteasome must be enlisted and controlled to allow it to escape apoptosis. Functioning on the cancer cell surface or in the extracellular milieu, secreted proteases (primarily metalloproteinases, serine p- teases, and cathepsins) determine the interactions of cells with their environments. Once considered simply as promoting tumour cell invasion through tissue barriers, proteolysis is now known to be integral to many aspects of cancer biology, including angiogenesis, regulation of the bioavailability of growth factors, cellular adhesion, cytokine/chemokine signalling, in?ammatory cell recruitment, and the mobilization of normal cells from their tissue compartments to act as accomplices in metastasis. The last decade has witnessed a revolution in our thinking concerning the role of extracellular proteolysis in cancer biology: this is the primary focus of this book.
In the context of the battle against cancer, the Degradome is important in three principal areas:- Cellular proteases and their inhibitors are components of the molecular machinery of malignancy, and thus are attractive as therapeutic targets. Importantly, we now appreciate that some proteases perform functions that antagonize tumour growth, and these are then anti-targets that must be avoided- Degradome genes are valuable as prognostic and diagnostic markers of disease that can improve the accuracy of conventional clinical and histopathological assessment- Cellular proteases are target molecules for improving tumour detection and imaging